Abstract
Purpose :
Retinoblastoma is the most common malignant intraocular tumor in children. If tumour invades the optic nerve, it poses a metastatic risk. Retinoblastoma develops after both alleles of the tumour suppressor RB1 gene at locus 13q14 have been mutated. While RB1 loss initiates the tumor development, additional somatic copy number alterations (SCNAs) can drive tumor progression of which MYCN is a well-known example. The SOX4 gene has recently been identified as a novel retinoblastoma driver candidate and has been identified as an important oncogene in other cancers. The purpose of this study is to evaluate, histopathologically, the level of expression of SOX4 in retinoblastoma and its correlation with optic nerve invasion.
Methods :
A total of 18 Retinoblastoma enucleated eyes were examined from the MUHC-McGill University Ocular Pathology & Translational Research Laboratory. Fully-automated immunohistochemistry using anti-SOX4 monoclonal antibody was performed. Slides were graded based on intensity (0=negative, 1=mild, 2=intense) and extent of staining (0=negative, 1=focal, 2=diffuse). In addition, the Retinoblastomas were evaluated on the presence or absence of optic nerve invasion (0= no invasion, 1=optic nerve).
Results :
Scores for each tumour sample were obtained by adding intensity and extent. The scores for optic nerve invasion and no invasion were compared in a two-sample t-test. The mean scores for the tumours with optic nerve invasion were higher (2.83) than that for no invasion (1.42). The difference in scores between each group was confirmed to be statistically significant (p<0.05).
Conclusions :
The results confirm that SOX4 correlates with optic nerve invasion and may have prognostic value. However, future experiments using a larger number of tumours is warranted. The identification of further driver genes such as SOX4 could lead to new targeted therapies in the treatment of retinoblastoma.
This is a 2020 ARVO Annual Meeting abstract.